The objective of this study is to increase our understanding of the formation, metabolism, excretion and plasma levels of estrone sulfate in man and several animal models to increase our knowledge of the physiological significance of this estrogen conjugate. The role of estrone sulfate in the overall biological action in man and the significance of this compound in other species is poorly understood. We have presented a series of experiments which will use several unique capacities of our laboratory to gain new information about the physiological significance of this compound. (a) We will use our recently developed specific radioimmunoassay for estrone sulfate to increase our understanding of the pattern of estrone sulfate levels in biological fluids of man and a number of primate species. We will study the alterations in estrone sulfate levels that occur in different physiological states, such as prepubertal, menopausal, pregnancy or disease states. (b) We will use our expertise in steroid dynamics and the study of regional formation and metabolism of estrogens and estrogen conjugates to identify the sites of formation and metabolism of estrone sulfate in the dog and man. This will increase our understanding of where estrone sulfate is formed for release into the blood and how the high blood levels of estrone sulfate are maintained.